Preliminary evidence indicates that non-pressor levels of anti-diuretic hormone (ADH, arginine vasopressin) is a chief determinant of extracellular fluid distribution between vascular and extravascular compartments, particularly when man is exposed to heat and/or exercise. To explore the hypotheses concerned with this extra-renal action of ADH we propose 3 general experiments. (a) Using combinations of rest, heat, exercise, hypohydration, and ADH injection, we will attempt to establish a relationship between ADH concentration and extracellular fluid distribution. The mechanics of the fluid shifts will be sought in an animal model (rat). Through pressure recordings (intra- and extra-vascular) we will first determine whole animal responses and by an isolated hind limb preparation explore the locus and route of ADH action, i.e., central or peripheral, direct or via the sympathetic nervous system. Finally, the hypothesis that the waxing and waning of ADH in the sub-fornical organ indicates a role in extracellular fluid distribution will be examined. Stereotaxic ablations of this organ and infusions of ADH and angiotensin II into the sub-fornical organ while the rat is hemodynamically monitored should adequately examine the hypothesis that the sub-fornical organ not only responds to angiotensin II and is involved in thirst but through ADH also determine the compartmentalization of extracellular fluid.